丙烯酰胺中毒后小鼠周围神经逆行性坏死的实验病理研究

目的 观察丙烯酰胺（ACR）中毒后变异的C57BL／Ola（Ola）鼠与正常的C57BL／6J（6J）鼠轴突逆行性坏死的病理改变及责任中鼠的不同点;探讨轴突与神经元损伤的关系。方法 利用光镜和电镜技术对腓神经、腓肠神经及背根神经节神经元的改变进行定性和定量分析。结果 光镜下6J鼠总纤维面积明显增大,纤维密度明显降低,大径纤维减少;轴突肿胀,髓鞘深染,形状不规划。背根神经节中一些亮细胞（A型细胞）核偏向一侧,胞浆内有一些暗颗粒。电镜下见轴突内神经微丝增多,线粒体堆积。背根神经节细胞胞浆内线粒体呈空泡样或凝聚样变性。Ola鼠未见明显改变。结论 Ola鼠对ACR所致的类化勒氏变性反应是延迟的,而6J鼠中毒后出现轴突肿胀、变性,电镜下神经微丝的聚集、线粒体堆积为特征;ACR先侵犯神经元,继之产生远端轴突变性。     

Ethylene oxide induces central-peripheral distal axonal degeneration of the lumbar primary neurones in rats

Wistar rats subjected to a single exposure lasting six hours to ethylene oxide (EO) at a concentration of 500 parts per million three times a week for 13 weeks developed ataxia in the hindlegs. Myelinated fibres in hindleg nerves and in the fasciculus gracilis showed axonal degeneration sparing the nerve cell body of the lumbar dorsal root ganglion and myelinated fibres of lumbar dorsal and ventral roots. These pathological findings are compatible with central-peripheral distal axonal degeneration. This is the first animal model of EO neuropathy to be histopathologically verified.     

Ethylene oxide induces central-peripheral distal axonal degeneration of the lumbar primary neurones in rats.

Wistar rats subjected to a single exposure lasting six hours to ethylene oxide (EO) at a concentration of 500 parts per million three times a week for 13 weeks developed ataxia in the hindlegs. Myelinated fibres in hindleg nerves and in the fasciculus gracilis showed axonal degeneration sparing the nerve cell body of the lumbar dorsal root ganglion and myelinated fibres of lumbar dorsal and ventral roots. These pathological findings are compatible with central-peripheral distal axonal degeneration. This is the first animal model of EO neuropathy to be histopathologically verified.     

Propylene oxide causes central-peripheral distal axonopathy in rats

In Wistar rats subjected daily to a 6-hr exposure of propylene oxide (PO) at a concentration of 1,500 ppm (5 times a wk for 7 wk), ataxia developed in the hindlegs. Myelinated fibers in hindleg nerves and in the fasciculus gracilis showed axonal degeneration, sparing the nerve cell body of the first sacral dorsal root ganglion and myelinated fibers of the first sacral dorsal and ventral roots. These pathologic findings are compatible with central-peripheral distal axonopathy. This is apparently the first animal model of PO neuropathy to be verified histologically.     

Determination of the exposure concentration of propylene oxide to produce neuropathy in rats

Although propylene oxide, which is similar in chemical structure to ethylene oxide, is expected to produce neuropathy, there is no convincing evidence of the degeneration of the peripheral nervous system. To determine the exposure concentration of propylene oxide necessary to produce neuropathy in male Wistar rats, we subjected them to repeated exposures of propylene oxide at concentrations of 500, 750, 1000, 1500 and 2000 ppm. The test rats were subjected to a single 6 hour exposure of propylene oxide at a concentration of 1500 parts per million 5 times a week for 3 weeks. They developed a significant decrease in body weight, abnormal posture of the hindlegs and axonal degeneration of myelinated fibers in the peroneal and sural nerves, the nerves to the soleus muscle, and in the fasciculus gracilis of the spinal cord. Therefore, it was concluded that propylene oxide induces neuropathy in rats characterized by axonal degeneration, similar to that produced by ethylene oxide, and that the exposure to the higher concentration of propylene oxide is more necessary to produce neuropathy than in the case of ethylene oxide neuropathy in rats.     

Propylene Oxide Causes Central-Peripheral Distal Axonopathy in Rats

In Wistar rats subjected daily to a 6-hr exposure of propylene oxide (PO) at a concentration of 1,500 ppm (5 times a wk for 7 wk), ataxia developed in the hindlegs. Myelinated fibers in hindleg nerves and in the fasciculus gracilis showed axonal degeneration, sparing the nerve cell body of the first sacral dorsal root ganglion and myelinated fibers of the first sacral dorsal and ventral roots. These pathologic findings are compatible with central-peripheral distal axonopathy. This is apparently the first animal model of PO neuropathy to be verified histologically.     

Effects of methylmercury on the motor and sensory innervation of the rat extensor digitorum longus muscle

This histochemical study examined the effects of chronic methylmercury (MeHg) intoxication on the motor and sensory innervation of extensor digitorum longus muscles. Light microscopic examination of silver-stained axons in the intramuscular nerve bundles of MeHg-treated rats showed Wallerian-like degeneration and a reduction in the number of nerve fibers. Disrupted axons were predominantly sensory because 22.2% of spindle afferents (Ia) and 90.0% of Golgi tendon organ (Ib) sensory fibers were completely degenerated whereas less than 1% of motor endings were totally destroyed. Partial disruption occurred in the cholinesterase and motor terminals of 13.7% of endplates. Our results demonstrated greater vulnerability of sensory nerves than of motor nerves to MeHg-induced degeneration. Thus, the abnormal reflexes, ataxia, and muscle weakness following MeHg poisoning appear related to reduction of proprioceptive feedback from muscles and tendons in addition to the documented lesions in the central nervous system.     

Morphometric analysis of normal human sural nerves for systematic clinical application]

To obtain normative data on the sural nerve for clinical evaluation of the pathologic process and severity of the various peripheral nerve disorders, a morphometric analysis was made on 30 control sural nerves from normal volunteers, and from patients and cadavers with no evidence of peripheral nerve involvement. The ages of volunteers, patients and cadavers ranged from 13 to 83 years. The data obtained included 1) the mean frequency of abnormal teased myelinated fibers and its upper limit value of 95% confidence interval, and 2) the mean densities of total, large and small myelinated fibers and of unmyelinated fibers and their lower limit value of 95% confidence interval for each decade. The linear correlation between the age and each of the frequencies of abnormal teased myelinated fibers and the densities of total, large and small myelinated fibers and of unmyelinated fibers were statistically significant (P less than 0.01). Therefore, the morphometric data obtained from the disease nerve should be compared with the normative data adjusted for the age of the subject described in this study.     

Evaluation of germanium dioxide neurotoxicity in rats and monkeys

Toxic side effects of germanium dioxide contained in drugs that promote health, include nephropathy, anemia and peripheral neuropathy. Although the neuropathy, which we are interested in, is believed to occur in the patients taking excessive amounts of germanium dioxide, the pathogenesis of such neuropathy is not well understood. Therefore, we studied whether germanium dioxide causes the degeneration of the peripheral nerve in rats and monkeys. Our results showed that in rats, germanium dioxide administered orally and intraperitoneally, 100 mg/kg per day, 3 days a week for 8 weeks and 400 mg/kg per day, once a week for 8 weeks, respectively, did not produce a degeneration of myelinated fibers in teased fiber preparations and Epon-embedded sections of the peripheral nerve. In two monkeys also, germanium dioxide, administered orally, 30 to 40 mg/kg per day, 5 days a week for 8 months, did not produce a degeneration of myelinated fibers of the sural nerve on biopsy, although our results revealed proteinuria and elevated blood urea nitrogen. Further studies are warranted to elucidate the pathogenesis of germanium dioxide induced neuropathy.     

Peripheral sensory neuropathy produced by a megadose of vitamin B6

Clinical cases of sensory neuropathy produced by a megadose of vitamin B6 have been reported in English literatures. We investigated the ordinary daily dosage and maximal dose of vitamin B6 widely adopted in Japan, and the amount of vitamin B6 per unit (per tablet, capsule or ampule) available in our medical practice. We concluded that in Japan it is very rare to administer such a large dose of vitamin B6 that produced sensory neuropathy described in the literatures. In our experimental study, Sprague-Dawley rats were intraperitoneally given a total amount of 14,000 mg/kg of body weight of pyridoxine hydrochloride in ten separate doses. They developed an ataxic gait. The occurrence of the degeneration of nerve cell bodies and peripheral axons of lumbar primary sensory neurons were histologically demonstrated. Although in Japan no clinical cases of neuropathy produced by a megadose of vitamin B6 have been reported to our knowledge, it is necessary to be aware of the possible occurrence of such neuropathy among patients with polyneuropathy of unknown etiology or who have been receiving vitamin B6 for a long time.     

Small axons relative to number of myelin lamellae in Charcot-Marie-Tooth disease 1A with peripheral myelin protein 22 gene duplication

In myelinated fibers of the sural nerves in Charcot-Marie-Tooth disease 1A (CMT 1A), with peripheral myelin protein (PMP) 22 gene duplication, it has been controversial whether axonal attenuation occurs or the myelin sheath thickens. Therefore, the relationship between the transverse axonal area and the number of myelin lamellae was morphometrically studied in myelinated fibers of the sural nerves in CMT 1A with PMP22 gene duplication to re-evaluate such relationships as are revealed in hereditary motor sensory neuropathy, type 1 without genetic diagnosis. In electron microscopic studies both the axonal circumference and natural log (ln) axonal area were significantly (P < 0.01) smaller in the CMT 1A group (n = 8) than in the control group (n = 9). Myelin lamellae numbers, however, were similar in both groups. In a regression analysis relating ln axonal areas to the numbers of myelin lamellae, ln axonal area in the CMT 1A group was significantly (P < 0.05) smaller than in the control group in myelinated fibers with the numbers of myelin lamellae equal to or over 40. Therefore, it was concluded that the axonal area was smaller in large-diameter myelinated fibers in the CMT 1A group than in the control group. We speculated on the existence of axonal attenuation due to the impaired effect of Schwann cells on myelinated axons in CMT 1A with PMP22 gene duplication.     

Effect of perinatal food deficiencies on the compound action potential evoked in sensory nerves of developing rats

The aim of this study was to analyze the possible alterations produced by inadequate perinatal food intake, in quantity (undernutrition) or quality (malnutrition), on the generation and propagation of the compound action potential (CAP) evoked in sensory sural nerves, during the postnatal development of the rat. Low intensity stimulation (2-3 times the threshold of the most excitable nerve fibers; xT) of the sural nerve evoked an early potential (CAP-A component) which is due to activation of low-threshold, fast-conducting myelinated group A afferent fibers. Meanwhile, at higher stimulus intensity (20-30T) it produced a second, long-lasting potential (CAP-C component) probably due to activation of high-threshold, slow-conducting group Adelta or C afferent fibers. Compared to control nerves, the CAP-A component, but not the CAP-C component of undernourished and malnourished nerves showed significant changes in amplitude, area, electrical threshold and conduction velocity (except absolute refractory period) at several postnatal ages. Our results may suggest that a relative large number of myelinated group A afferent fibers in the sural nerve of undernourished and malnourished animals suffer severe alterations on their electrophysiological properties of generation and propagation of the action potential during the postnatal development of the rat.     

Effect of Perinatal Food Deficiencies on the Compound Action Potential Evoked in Sensory Nerves of Developing Rats

The aim of this study was to analyze the possible alterations produced by inadequate perinatal food intake, in quantity (undernutrition) or quality (malnutrition), on the generation and propagation of the compound action potential (CAP) evoked in sensory sural nerves, during the postnatal development of the rat. Low intensity stimulation (2–3 times the threshold of the most excitable nerve fibers; X T) of the sural nerve evoked an early potential (CAP-A component) which is due to activation of low-threshold, fast-conducting myelinated group A afferent fibers. Meanwhile, at higher stimulus intensity (20–30T) it produced a second, long-lasting potential (CAP-C component) probably due to activation of high-threshold, slow-conducting group Aδ or C afferent fibers. Compared to control nerves, the CAP-A component, but not the CAP-C component of undernourished and malnourished nerves showed significant changes in amplitude, area, electrical threshold and conduction velocity (except absolute refractory period) at several postnatal ages. Our results may suggest that a relative large number of myelinated group A afferent fibers in the sural nerve of undernourished and malnourished animals suffer severe alterations on their electrophysiological properties of generation and propagation of the action potential during the postnatal development of the rat.     

Neurotoxicity of 1-bromopropane in rats

Neurotoxicity of 1-bromopropane (1-BP) used as an alternative solvent of fluorocarbons was experimentally studied. Eight rats in the experimental group were exposed to 1-BP at 1500 ppm for six hours a day, five days a week for four weeks in an exposure chamber. Another eight rats in the control group were exposed to room air in a similar exposure chamber as those in the experimental group. During the latter half of the fourth week of exposure, all the rats in the experimental group showed a loss of body weight and ataxic gait compared with control rats. At the end of the fourth week, the rats in both groups were perfused through the ascending aorta and fixed. The cerebellum, medulla oblongata, spinal cord and peripheral nerve were processed for histopathological studies. No statistically significant difference in the frequency of axonal degeneration in both peroneal and sural nerves was found between the experimental and control groups. In the cerebellum, the frequency of degeneration of Purkinje cells in both the vermis and hemisphere was higher in the experimental group than in the control group (P < 0.05). There was no significant difference in the frequency of myelin ovoids in the fifth thoracic and in the third cervical posterior columns of the spinal cord between control and experimental groups. There was also no significant difference in the frequency of axonal swelling in the nucleus gracilis of the medulla oblongata between control and experimental groups. Ataxic gait was considered to be induced by degeneration of Purkinje cells in the cerebellum due to 1-BP exposure. However, degenerative findings of nerve fibers in the peripheral nerve, spinal posterior column and nucleus gracilis of the medulla oblongata due to 1-BP exposure were not evident. At the end of the fourth week of exposure, rats in the experimental group showed loss of body weight and markedly decreased motor activities, and it was considered that they would die if we continued the exposure into the fifth week. Therefore, we feel that our experimental schedule should be reconsidered before undertaking any further studies on the peripheral nerve toxicity of 1-BP.     

Assessment of the peripheral, central, and autonomic nervous system function in styrene workers.

To investigate the effects of styrene exposure on peripheral, central, and autonomic nervous system functions in man, we measured the distribution of nerve conduction velocities (DCV), short-latency somatosensory evoked potentials (SSEP), and variability in electrocardiographic R-R interval (CVRR) as well as conventional sensory and motor median nerve conduction velocities (SCV and MCV) in eleven styrene-exposed workers. The styrene workers' urinary phenylglyoxylic acid levels ranged from 31 to 419 (mean 169) mg/g creatinine at the end of the work shift on the examination day (estimated exposure to styrene of 22 ppm in air). Control subjects, matched to each styrene worker by sex and age, were selected from healthy adults without cardiovascular, neurologic and other potentially confounding disorders. In the styrene workers, we found that the V80 velocity of the DCV, below which 80% of active nerve fibers lie, and the SCV were both significantly slowed; the CVRR was also significantly reduced. There were no significant differences in SSEP latencies, MCV, or heart rate between the exposed workers and controls. These data, despite the small sample size, suggest that styrene affects the faster myelinated fibers of the peripheral sensory nerves, and that it also affects autonomic nervous activity.     

Ultrastructural changes of cutaneous nerves in scleroderma.

Ultrastructural changes in cutaneous nerves of 38 patients with progressive scleroderma and eight patients with circumscribed scleroderma are described in the present study. Changes in the myelinated as well as in the unmyelinated fibers were observed in all cases. Myelinated fibers exhibited progressive disintegration of their myelin sheaths. Edema of the cytoplasm and various lesions of the organelles were observed in the Schwann cells. The basal membranes of both myelinated and unmyelinated fibers were irregularly thickened and flimsy in appearance. The axis cylinders were affected to a lesser extent. Edema of the axoplasm, and, less often, reduction of the number of neurofibrils and microtubules were observed there. Sometimes, the nerve fibers were enwrapped compactly by a considerable amount of collagen fibrils. The observed changes of the peripheral skin nerves are very often secondary. They are the morphologic basis of a limited or generalized neuropathy which sometimes develops.     

Electroneurographic findings in patients with solvent induced central nervous system dysfunction.

The function of the peripheral nervous system was examined in a group of 32 men aged 30-65 (mean 49) with diagnosed solvent induced chronic toxic encephalopathy. The subjects were examined at the time of diagnosis and 26 were re-examined after a follow up period of 22-72 months (mean 40) and compared with a group of 50 unexposed male workers aged 27-64 (mean 42) with appropriate adjustment for age. All subjects were carefully scrutinised for alcohol abuse and other neurological diseases. The results of motor fibre neurography disclosed no difference between the groups. Nevertheless, a significant decrease in motor conduction velocity was found in the patients at follow up. Sensory fibre neurography showed signs of slight axonal degeneration with significantly decreased sensory nerve action potential amplitudes in the median and sural nerves; these amplitudes increased during follow up. The duration of sensory nerve action potentials was longer in the exposed group for the median and the sural nerves. The percentage of late components was significantly higher in the median nerve. The warm-cold sensitivity in the exposed group also indicated a slight sensory dysfunction with statistically significant wider detection limits.     

Neurotoxic effects of mercury--a review.

The significant literature concerning the neurotoxic effects of mercury, biochemical, physiological, and morphological, is reviewed. Mercury was found to penetrate and damage the blood-brain barrier very rapidly, leading to a dysfunction of the blood-brain barrier system. Both biochemical and electron-microscopic histochemical analysis revealed that, intracellularly, mercury was bound to the membranous organelles such as mitochondria, endoplasmic reticulum, Golgi complex, nuclear envelopes and lysosomes. Only very minimal amounts of mercury were found within the nucleus. Biochemical and cytochemical studies also indicated that drastic reduction of neuronal RNA and protein synthesis occurred in mercury-intoxicated animals. Reduction of the protein synthesis was believed to lead to eventual cell death in these neurons. A regain in the neuron RNA level was also observed in prolonged intoxication with mercuric bichloride. Such an observation could also be correlated with the increasing tolerance to mercury toxicity by these animals. Disturbance of the enzymatic systems in the glycolytic pathway in the brain was also reported in mercury-poisoned animals. Neurophysiological study demonstrated abnormal excitation spikes in the mercury-intoxicated neurons. The suggestion that neuronal cell body injury preceded axonal injury was made. It was also suggested that the large-caliber myelinated fibers were more vulnerable than the smaller nerve fibers to mercury toxicity. Pathological findings on Minamata disease were summarized. In experimental models, it was found that the sensory neurons in the spinal ganglia and granule cells in the cerebellum were most vulnerable to mercury poisoning. Ultrastructural studies indicated that vacuolar degeneration of the neurons was mainly associated with inorganic mercury intoxication, while coagulative type of degeneration was found mostly in organic mercury poisoning. Degenerative changes in the nerve fibers were also observed. Based on the biochemical, physiological, and pathological findings on mercury intoxication, a working hypothesis on the pathogenetic mechanism of mercury on the nervous system is proposed.     

Structural aspects of experimental carbon disulfide neuropathy

Summary In white rats exposed to CS₂ vapors (at the average concentration of 1.5 mg per liter of air) over 1 to 15 months, the progressive development of structural lesions was studied in the selected areas of the central and peripheral nervous system. Gradual destruction of myelinated fibers within the white matter of spinal cord and in the peripheral nerves was observed. Morphological alterations of the body of the nerve cells were also encountered, but their pathologic nature and their relation to the exposure were disputable even at the stage of advanced CS₂ induced myelo- and neuropathy.This investigation has been done under the Polish-American agreement No. 05-003-3 with the Occupational Health Program, U.S. Public Health Service.     

足底内侧神经检测在2型糖尿病周围神经病诊断中的价值分析

目的 探讨足底内侧神经检测对糖尿病周围神经病的诊断价值.方法 选取2020年1—7月就诊于大连市中心医院内分泌科,明确诊断2型糖尿病的109例患者为研究对象,应用肌电诱发电位仪对患者胫神经、足底内侧神经、腓肠神经、腓浅神经进行检测.结果 足底内侧神经检出异常率均高于腓肠神经、腓浅神经和胫神经H反射及F波异常率,差异均有...